tbuckley/cabot-search huggingface dataset:
PB2146: CHARACTERISTICS AND OUTCOMES OF COVID-19 IN PATIENTS WITH PLASMA CELL DISORDERS DURING THE FIRST OMICRON WAVE IN BEIJING SINCE DECEMBER 2022: A RETROSPECTIVE STUDY AT A TERTIARY CENTER
Authors: Qing He, Xuelin Dou, Yang Liu, Nan Peng, Lizong Gong, Lei Wen, Jin Lu
Journal: HemaSphere (2023)

Topic: 14. Myeloma and other monoclonal gammopathies - Clinical Background: The wave of COVID-19 infections with Omicron variant have reached the peak in December 2022 in Beijing. Aims: We described patients’ characteristics and investigated factors associated with adverse outcome during first month of the wave. Methods: Data of patients with plasma cell disorders (PCDs) infected with COVID-19 during the first month since Dec 7th was retrospectively collected. Results: One-hundred and four patients with a median age of 65 years were included. Multiple myeloma (74%, n=77) and primary amyloidosis (16.3%, n=17) were the two most common plasma cell disorders. The all-cause mortality was 4.8% (n=5), with 4 patients died of COVID-19 and 1, of the relapsed of multiple myeloma. Overall, 28(26.9%) of the patients were hospitalized, 7(25%) of whom received mechanical ventilation with 6 patients received bilevel positive airway pressure (BiPAP) and 1 with intubation. 1(3.6%) patient developed venous thromboembolism (VTE) and 7(25%) patients developed secondary fungal or bacterial infections. Severe or critical COVID-19 was developed in 17.3% of patients(n=18). In multivariate logistic analysis, age was the only independent risk factors (OR=1.14 CI 95%:1.06-1.26, p = 0.002) associated with the development of severe/critical disease, while vaccination status, immunoparesis, comorbid renal or heart disease, high-risk cytogenetics, or the application of anti-CD38 monoclonal antibody were not associated factors. In multivariate cox analysis in severe/critical group patients, albumin (HR=18.29; CI 95%: 1.82-183.44, p=0.013) and lactic dehydrogenase (HR=0.08; CI 95%: 0.01-0.65, p=0.018) were risk factors associated with COVID-19 negative conversion time. Summary/Conclusion: In patients with PCDs, the all-cause mortality was 4.8%(n=5). 18 patients (17.3%) developed severe/critical COVID-19. Only advanced age was associated with the development of severe/critical disease. In severe/critical group patients, albumin and lactic dehydrogenase were risk factors for COVID-19 negative conversion time. Keywords: Multiple myeloma, COVID-19
PB2075: HOW EFFECTIVE ARE LEPTIN GENE POLYMORPHISMS AND METHYLATION DURING THE COURSE OF MULTIPLE MYELOMA (MM)?
Authors: Istemi Serin, Yasemin Oyaci2, Mustafa Pehlivan, Ilknur Demir, Burcak Demir, Tahir Alper Cinli, Osman Yokus, Sacide Pehlivan
Journal: HemaSphere (2023)

Topic: 13. Myeloma and other monoclonal gammopathies - Biology & Translational Research Background: Leptin is mainly produced from adipose tissue and released into the circulation. Circulating leptin binds to the leptin receptor (LEPR) in the brain, which activates signaling pathways that inhibit feeding and promote calorie expenditure. The leptin receptor (LEPR, also known as Ob-R) gene is located at 1p31. DNA methylation consists of addition a methyl group at position 5′ of the pyrimidine ring of the cytosines upstream of a guanine (dinucleotide CpG) catalyzed by DNA methyltransferases. Methylation of cytosine in CpG sites is an important epigenetic modification way that could suppress the gene expression. Aims: This study was conducted to reveal the role of leptin (-2548 G/A, rs7799039) and LEPR (-668 A/G, rs113711) gene polymorphisms in patients diagnosed with multiple myeloma (MM). Methods: Patients who were diagnosed with MM and followed-up in our clinic between January 2010 and January 2022 were included in the study. The genotypes of the leptin (-2548 G/A, rs7799039) and LEPR (-668 A/G, rs113711) genes were statistically compared between patients and healthy controls. Additionally, the statistically significant effects of these genotypes on survival were examined. In addition, the methylation status of the patients was compared to the healthy control group, and the effect on survival was evaluated. Results: A total of 300 patients diagnosed with MM and 170 individuals to form a healthy control group were included in this study. In the statistical analysis performed to investigate the effect of leptin and LEPR gene polymorphisms on disease susceptibility, GA and AA genotypes of leptin gene were found to be significantly higher in the patient group compared to healthy controls. In the statistical analysis for -31 NT and -51 NT methylation of the leptin gene, -51 NT methylation was found to be significantly higher in healthy controls (p=0.002). In the survival analysis, progression-free survival (PFS) of patients with the GG genotype of LEPR gene was found to be significantly shorter compared to others, there was no effect on the overall survival. In the multivariate analysis, it was revealed that the PFS of patients with the GG genotype of LEPR gene was 2.02 times shorter compared to others (RR: 2.017; CI: 1.191-3.418, p=0.009). Summary/Conclusion: MM and leptin polymorphisms have significant features in terms of both disease susceptibility and treatment response. Table 1. Comparison of leptin gene variants between patients diagnosed with MM and healthy controlsTable 2. Comparison of PFS and OS with prognostic factors of patients diagnosed with MMTable 3. Multivariate analysis of 300 patients with MM (Cox proportional hazard model backward)Keywords: Survival, Multiple myeloma, Epigenetic, Leptin receptor
PB2396: HDACI COMBINED WITH LB100 PROMOTES THE OCCURRENCE OF FERROZOSIS IN CTCL
Authors: Wenyu Shi
Journal: HemaSphere (2023)

Topic: 20. Lymphoma Biology & Translational Research Background: Cutaneous T-cell lymphoma (CTCL) is a type of non-Hodgkin’s lymphoma that originates in the skin due to clonal proliferation of T-lymphocytes. The current first-line treatment regimen for PTCL is CHOP, which is effective for ALK-positive ALCL but not very friendly for CTCL and other subtypes of PTCL. HDAC inhibitors have shown promising results as a second-line treatment for PTCL, and their anti-tumor mechanisms are being explored. Aims: In this study, we investigated the role of HDAC inhibitors in enhancing ferroptosis, a newly discovered mode of cell death that is characterized by mitochondrial membrane lipid peroxidation, ferritin phagocytosis, and the release of ferrous ions leading to cell death. Methods: We evaluated ferroptosis-related molecules using WB and qPCR and observed the effects of HDAC inhibitors on ferroptosis using electron microscopy, PGSK probe, and focused microscopy. We also assessed the effects of HDAC inhibitors combined with ferroptosis inducer on apoptosis, cell cycle arrest, viability, and proliferation using various assays, including flow cytometry, CCK8, and Edu. Finally, we tested the therapeutic potential of the combination in a SD rat transplantation tumor model. Results: We found that HDAC inhibitors significantly enhance ferroptosis inducer-mediated ferroptosis in PTCL. HDACI+LB100 promotes cellular lipid peroxidation and iron zosis by inhibiting the cholesterol synthesis pathway. The WB and qPCR results showed that the expression of GPX4, FPN1, HMGCS1, HMGCR, MVK and so on were down-regulated. Cholesterol levels are reduced and cellular reactive oxygen species levels are significantly increased. Under electron microscopy, mitochondrial membrane was seen to shrink, the density increased, and the mitochondrial crest decreased significantly. The combination also led to increased apoptosis levels and down-regulation of BCL-2 and Caspase3. P-H2AX expression is upregulated. CyclinD1 is significantly downregulated, activating the JNK signaling pathway, resulting in G2/M phase arrest. The combination group also showed a significant reduction in tumor volume in the transplantation tumor model. Summary/Conclusion: Our study suggests that HDAC inhibitors combined with LB100 is a promising therapeutic strategy for the treatment of PTCL. The enhanced ferroptosis and apoptosis, as well as the downregulation of CyclinD1 and reduced cell viability and proliferation, support the potential of this approach as a treatment option for CTCL and other subtypes of PTCL. Keywords: T cell lymphoma
PB2226: HIGH RISK LANGERHANS CELL HISTIOCYTOSIS (LCH) IN CHILDREN: THE ROLE OF CLADRIBINE SALVAGE IN IMPROVING THE OUTCOME. A SINGLE CENTER EXPERIENCE
Authors: Mohamed Sedky Sedky, Asmaa Hamouda, Hala Taha, Iman Zaky, Omayma Hassanain, Alaa Elhaddad
Journal: HemaSphere (2023)

Topic: 16. Myeloproliferative neoplasms - Clinical Background: Failing 1st line treatment in multi-system high risk organs (RO+) pediatric Langerhans cell histiocytosis (LCH) has the highest mortality. Aims: We aim to present the outcome of salvage in RO+ LCH and to show the impact of cladribine/ aracytine based regimen (2-CdABR). Methods: Sixty-seven RO+ LCH patients, treated between mid-2007 and end 2019 were retrospectively analyzed. 1st line treatment failure was either due to Disease Progression (DP) following induction (Group I) or afterwards Reactivation (REA) following better status achievement (Group II). Both groups were subjected to salvage with or without 2-CdABR. Results: Forty-two patients failed 1st line: Group I n=22. Of them 9 patients received 2-CdABR where 4 died. Otherwise, all the other 13 patients died except one. Group II n=20. Of them 8 patients received 2-CdABR where 4 died. Otherwise, all the other 12 patients survived except 3. The overall survival (OS) of the whole 67 RO+ patients is 65 % CI=11.6, while event free survival (EFS) is 36% CI=11.6. The OS of those undergoing DP 27% CI=18.8 versus REA 65% CI=23.1 versus those without treatment failure 96% CI=7.6 p˂ 0.001. Out of the 42 failing patients, the OS of 2-CdABR is 53% CI=25.7, versus other regimen 59 % CI=23.3, vs no salvage 0 % p˂ 0.001. In these 22 DP patients, the OS of 2-CdABR is 56% CI=32.5, versus other regimen 20 % CI=35, versus no salvage 0%, p 0.003. While in those 20 REA patients, the OS of 2-CdABR is 33% CI=38 versus other salvage regimen 83.3 % CI=25 p value 0.66. Summary/Conclusion: 2-CdABR rescued DP RO+LCH in relation to regimen without. Moreover, its impact on REA remains controversial in relation to other salvage regimen. Keywords: Salvage chemotherapy, Langerhans Cell Histiocytosis, Cladribine, Risk factor
PB2419: THE OUTCOME OF VIRAL HEPATITIS-C INFECTION ON HEMATOLOGICAL MALIGNANCIES AFTER AUTOLOGOUS BONE MARROW TRANSPLANTATION IN EGYPT
Authors: Salma Elashwah, MA Elbaiomy, Mohamed Samra, Shaimaa El-Ashwah, Raafat Abdelfattah, Gamal Fathy, Sameh Shamaa
Journal: HemaSphere (2023)

Topic: 22. Stem cell transplantation - Clinical Background: Autologous bone marrow transplantation (ABMT) is the cornerstone of many hematological disorders. HCV-infected patients who undergo ABMT are at risk for a variety of HCV infection-related complications. Furthermore, acute exacerbation may occur during and after transplantation. Hence, the need for studies on the impact of HCV on ABMT is imperative. Aims: The primary objective of this study is to determine the outcome of HCV patients with hematological malignancies after ABMT, including toxicity and disease-free survival (DFS). The secondary objective is to identify if there is a difference in overall survival (OS) between HCV-positive and negative patients after ABMT. Methods: This is a retrospective study that included 100 HCV positive patients with hematological malignancies (lymphoma and myeloma) who received ABMT compared to cross matched 100 HCV negative patients based on age, gender, and disease status at transplant. They were attending the outpatient clinics for follow up in Nasser Institute and Sheikh Zayed Specialized Hospital, Egypt. Acute exacerbation of chronic HCV infection is defined as ≥ 3-fold increase in basal ALT level without recent history of blood transfusion, infection, hepatic infiltration, or use of hepatotoxic drugs. Results: This study showed that the mean age of patients was 44.5 (± 12.5) years. They were 154 males and 46 females. The most common reasons for ABMT were multiple myeloma (40%), non-hodgkin lymphoma (33.5%), and hodgkin lymphoma (26.5%). There was a significant increase in the frequency of NHL among the HCV-positive group (p 0.007). Pre-transplant AST and ALT levels were significantly higher in the HCV-positive group than in the HCV-negative group (p 0.001 and 0.001, respectively). There were significant differences in the post-transplant outcome regarding serum bilirubin level and the incidence of acute exacerbation between the HCV- positive and HCV- negative study groups (p 0.044 and 0.049, respectively). The HCV-positive group received a significantly higher number of platelet units transfusion than those in the HCV-negative group (p 0.001). The median duration of hospital stay was significantly prolonged in the HCV-positive group compared to the HCV-negative group (p 0.024). DFS was significantly shorter in HCV-infected individuals (p 0.048), while OS was comparable between both groups (P 0.259). Summary/Conclusion: We concluded that, while the HCV-negative arm had a better result than the positive arm, HCV positivity is not a contraindication to ABMT. Keywords: Hepatitis C virus, Multiple myeloma, Autologous bone marrow transplant, Lymphoma
PB2434: DONOR CELL INDUCING IMMUNE-TOLERANCE IMPROVED ENGRAFTMENT IN TΑΒ+ CELL DEPLETED HSCT IN PATIENTS WITH THALASSEMIA MAJOR
Authors: Jianyun Liao, Chaoke Pu, Lan He, Yuelin He, Jujian He, Dan Chen, Bo Lyu, Weiwei Zhang, Haoran Tang, Xinrui Liu, Chunfu LI
Journal: HemaSphere (2023)

Topic: 22. Stem cell transplantation - Clinical Background: Hematopoietic stem cell transplantation (HSCT) still was a cure way proved over a long period of time in patients with thalassemia major (TM), but it usually resulted in severe graft versus host disease (GVHD). Although low GVHD have been observed in Tαβ+ cell depleted HSCT (TDH) from haploidentical donors, graft failure (GF) was high in patients with TM. Aims: For preventing the high GF in TM-TDH. Methods: Total 113 TM patients received TDH from April 2021 to Dec. 2022 in Taixin BMT center. Median age was 7 (2-19) year old and male: female was 75:38. Induction of donor cell immune-tolerance included ATG on -day 21 and 3-Gy TBI on -day 11, donor lymphocytes (2*108/kg) infusion on -day10, and two dose cyclophosphamide (Cy) on -day8 to 7. Uninterruptedly, conditioning regimen included busulfan, fludarabine, thiotepa and Cy was given. Prophylaxis of GVHD included short-term (< 6 months) low dose tacrolimus or sirolimus with or without MMF. The mean dose of infused CD34+ cells was 32.02 (14.25-61.12) *106/kg. Tab+ cells dose was aimed to 2.0*105/kg. Results: One hundred nine patients acquired the engraftment with 16 (9-48) day, 10 (5-22) day, and 11(1-23) day median time corresponding to ANC to 0.5x10e9/L, platelet to 20x10e9/L and HB 80g/L, respectively. GF occurred on four patients. Two of four patients with GF received salvage alternative donor 2nd HSCT on +day 19 and 32, respectively, and live with thalassemia-free. One patient infused back cryopreserved auto-PBSC and live with TM. Two patients died. One patient with GF died of suspicious virus infection on +day11 and the another with bronchiolitis obliterans died of infection on +day 254. With 278-day median follow-up, overall survive (OS) and thalassemia-free survive (TFS), GF and transplant-related mortality (TRM) were 97.7%, 95.1, 3.5% and 2.3% (Fig.), respectively. In consideration of 2 patients received 2nd transplant being TFS, so, TFS was 96.8%, in total, for 113 TM patients in the current study. No acute GVHD III-IV and >I chronic GVHD occurred in all patients. VOD was mild and little. Conclusion: Current study proved that donor cell inducing immune-tolerance improved engraftment in TM-TDH. Fig.1 Curve of OS, TFS, TRM and Rejection in TM-TDHKeywords: Stem cell transplant, T cell depletion, Pediatric, Thalassemia
PB2041: COMPARISON OF ELTROMBOPAG AND AVATROMBOPAG IN THE TREATMENT OF REFRACTORY/RELAPSED APLASTIC ANEMIA, A SINGLE CENTER STUDY IN CHINA
Authors: Zhuxin Zhang, Qinglin Hu, Chen Yang, Miao Chen, Bing Han
Journal: HemaSphere (2023)

Topic: 12. Bone marrow failure syndromes incl. PNH - Clinical Background: Eltrombopag (EPAG), one of the thrombopoietin receptor agonists (TPO-RAs), has been approved for refractory/relapsed aplastic anemia (AA), however, data on avatrombopag (AVA), another TPO-RA are limited, let alone the comparison between the two TPO-RAs. Aims: To evaluate and compare the efficacy and safety between EPAG and AVA treatment in relapsed/refractory AA patients in a real-world setting. Methods: Data from patients diagnosed with acquired refractory/relapsed and treated with either EPAG or AVA in our center were retrospectively collected. Refractory/relapse was defined as those who were refractory/relapsed to immunosuppressant (IST) for at least 6 months before EPAG/AVA. Patients had to be treated with EPAG or AVA alone for at least 6 months before evaluation if not responded. Baseline characters, overall response (OR) and complete response (CR), relapse, adverse events, and factors that may affect efficacy were analyzed. Results: 75 patients were enrolled in the study, including 45 patients treated with EPAG and 30 patients treated with AVA. No difference in baseline characters between the two groups except patients with AVA had more percentage of abnormal renal or liver function compared with those with EPAG (p=0.036). No significant difference was found in time to response (P=0.256) or OR/CR rate at 1st/2nd/3rd/6th month between the two groups (P＞0.05). Patients treated with AVA who had platelet response had a shorter median time to maximum platelet level than EPAG (P=0.009), and had a higher platelet level at 2nd month (P=0.022). However, no significant difference was found in the platelet level at other time points between the two groups (P＞0.05). AVA had less adverse events than EPAG (P=0.046). Under compatible follow-up time (P=0.572), no difference was found between EPAG and AVA group in relapse (P=1.000) or clone evolution (P=0.637). No predictive factors for overall response at 6th month were found either for EPAG or AVA. Summary/Conclusion: With worse liver and kidney function, AVA had similar OR/CR rate but had shorter time to maximum platelet response in responders and less adverse events for patients with relapsed/refractory AA. Key words: relapsed/refractory, aplastic anemia, avatrombopag, eltrombopag, effects Off-Label Disclosure: In the presented study, avatrombopag was off-label used in relapsed/refractory aplastic anemia patients. Keywords: Aplastic anemia, relapsed/refractory
PB2348: OUTCOME OF VERY ELDERLY DIFFUSE LARGE B CELL LYMPHOMA, SINGLE CENTER EXPERIENCE, RETROSPECTIVE ANALYSIS
Authors: Jee Hyun Kong, Jaeyeon Jang, Yundeok Kim
Journal: HemaSphere (2023)

Topic: 19. Aggressive Non-Hodgkin lymphoma - Clinical Background: With rapid growth of the elderly population, elderly diffuse large b cell lymphoma (DLBCL) patients have been increased. However, there was no enough evidence of that R-CHOP is safe and standard chemotherapy in very elderly DLBCL patients who had many comorbidities. Aims: We evaluated treatment pattern and outcome of very elderly DLBCL patients, and analyzed the relationship between initial clinical characteristics including anthropometric data, cumulative illness rating scale-geriatric(CRIS-G), international prognostic index (IPI) or dose density of chemotherapy, and treatment outcomes of very elderly DLBCL patients, retrospectively. Methods: We included patient who were diagnosed with DLBCL at age 80 or older at Wonju Severance Christian Hospital between January 2010 and June 2022, and had consented to provide their medical record. If date of chemotherapy or dose were not available, then that case was excluded. Results: A total 44 patients were included. The median age was 83 (80-94) years old and 75% were female. Median BSA and BMI were 1.5m2 and 22.9kg/m2 respectively. Median CRIS-G score was 5.5 (0-19). Half of patients’ ECOG were 0-1. Extranodal disease was identified in 20 (45.5%) patients and 4(9.1%) had bulky disease. LDH was normal in 16 (36.4%). Sixteen patients (36.4%) had localized disease (Stage I and II). IPI was available at 35 patients, and 15 (24.1%) were high risk. Eleven patients (25%) were germinal center B-cell type. Thirty-two patients (72.7%) were received chemotherapy (Figure 1), and 2 of them received 2nd line chemotherapy. Front line treatments were R-CHOP(n=27), R-CHOP followed by radiotherapy(n=3), and bendamustine/rituximab (BR)(n=2). Response was not evaluated 9 patients. Complete response (CR) and partial response (PR) was achieved in 18 (56.3%) and 6 (18.8%) patients, respectively. 2 patients (6.3%) were refractory to treatment. Except 1 patient who received BR, all patient received reduced dose of chemotherapy, and the median mean dose intensity was 50% (50-100). Only 8 patients completed treatment schedule, other 24 patients interrupted their treatment due to following reasons:1. patient or doctor’s choice (n=5), 2. disease progression(n=3), 3. pneumonitis due to R-CHOP(n=4), 4. cardiac adverse event (AE)(n=4), 5. Other AEs including diverse infections(n=7), 6. femur fracture due to accident. Overall survival at 3-year was 59%. Sex, BMI, BSA, extranodal disease, bulky disease, ECOG, LDH, bone marrow involvement, CRIS-G, DLBCL type and dose density of chemotherapy did not affect OS in this study. Summary/Conclusion: Although most patients received reduced dose of chemotherapy, only 1/3 patents completed scheduled treatment. Moreover, the main reason of stopping therapy was adverse event. Thus, novel therapy with low toxicity for very elderly DLBCL is required.Keywords: DLBCL, Elderly, Chemotherapy